Magnetoliposomes: opportunities and challenges

Combining liposomes with magnetic nanoparticles is an intriguing approach to create multifunctional vesicles for medical applications, which range from controlled drug delivery vehicles to diagnostic imaging enhancers. Over the past decade, significant effort has been invested in developing such hybrids - widely known as magnetoliposomes - and has led to numerous new concepts. This review provides an overview on of the current state of the art in this field. The concept of magnetic fluid hyperthermia and stimuli-responsive nanoparticles for drug delivery is briefly recapitulated. The materials needed for these hybrids are addressed as well. The three typically followed approaches to associate magnetic nanoparticles to the liposomes are described and discussed more in detail. The final chapters are dedicated to the analytical methods used to characterize these hybrids and to theoretical considerations relevant for bilayer-embedded nanoparticle

Serum Metabolites Responding in a Dose-Dependent Manner to the Intake of a High-Fat Meal in Normal Weight Healthy Men Are Associated with Obesity

Although the composition of the human blood metabolome is influenced both by the health status of the organism and its dietary behavior, the interaction between these two factors has been poorly characterized. This study makes use of a previously published randomized controlled crossover acute intervention to investigate whether the blood metabolome of 15 healthy normal weight (NW) and 17 obese (OB) men having ingested three doses (500, 1000, 1500 kcal) of a high-fat (HF) meal can be used to identify metabolites differentiating these two groups. Among the 1024 features showing a postprandial response, measured between 0 h and 6 h, in the NW group, 135 were dose-dependent. Among these 135 features, 52 had fasting values that were significantly different between NW and OB men, and, strikingly, they were all significantly higher in OB men. A subset of the 52 features was identified as amino acids (e.g., branched-chain amino acids) and amino acid derivatives. As the fasting concentration of most of these metabolites has already been associated with metabolic dysfunction, we propose that challenging normal weight healthy subjects with increasing caloric doses of test meals might allow for the identification of new fasting markers associated with obesity

Postpartum Hemorrhage: Differences in Definition, Data and Incidence

Introduction Postpartum hemorrhage (PPH) remains a major cause of morbidity and mortality worldwide. Geo-temporal comparisons of in-hospital PPH incidence remain a challenge due to differences in definition, data quality and the absence of accurate, validated indicators. Objectives and Approach To compare the incidence of PPH using different definitions to assess the need for a validated indicator. Singleton births from 2014-2016 at Lausanne University Hospital, Switzerland, were included. PPH was defined based on 1) clinical diagnosis using International Classification of Diseases (ICD-10-GM) PPH diagnostic codes, 2) volume of blood loss ≥500ml for vaginal births and ≥1000ml for cesareans 3) peripartum Hb change >2g/dl in vaginal births and ≥4g/dl in cesareans and 4) fulfillment of criteria from definition one, two or three. Data were extracted from hospital discharge data and linked with electronic health records. Results There were 2529, 2660 and 2715 singleton births in 2014, 2015 and 2016, respectively, 28.8% were cesareans. Peripartum change in Hb was available for 17% of births. The incidence (95% CI) of PPH in 2014, 2015 and 2016 was, respectively: 1)6.0% (5.1, 7.0), 6.3% (5.4, 7.3) and 7.9% (6.9, 9.0) based on diagnostic codes; 2)7.9% (6.8, 9.0), 7.1% (6.2, 8.2) and 7.2% (6.3, 8.3) based on blood loss volumes; 3)2.4% (1.8, 3.1), 2.7% (2.1, 3.4) and 3.5% (2.9, 4.3) based on change in Hb; 4)11.3% (10.1, 12.6), 10.4% (9.3, 11.6) and 11.0% (9.9, 12.3) based on the combined definition. Differences in PPH incidence by year between definitions one and four, two and four and three and four were all statistically significant (McNemar p-values Conclusion/Implications Incidence varied widely according to definition and data availability, not to mention data quality. Our results highlight the need for a validated PPH indicator to enable monitoring. Future prospects include the validation of a diagnostic code based PPH indicator aided by text mining in electronic health records

Catechol-derivatized poly(vinyl alcohol) as a coating molecule for magnetic nanoclusters

Surface functionalization of superparamagnetic iron oxide nanoparticles (SPIONs) remains indispensable in promoting colloidal stability and biocompatibility. We propose a well-defined and characterized synthesis of a new catechol-functionalized RAFT (reversible addition–fragmentation chain transfer) poly(vinyl alcohol) polymer, which can be anchored onto hydrophobic SPIONs via a one-pot emulsion ligand exchange process. Both single and clustered nanoparticles are obtained and can be separated from each other. As clustered SPIONs are receiving increasing attention, this new macroligand might be of considerable interest for both basic and applied sciences

Beyond global charge: role of amine bulkiness and protein fingerprint on nanoparticle–cell interaction

Amino groups presented on the surface of nanoparticles are well‐known to be a predominant factor in the formation of the protein corona and subsequent cellular uptake. However, the molecular mechanism underpinning this relationship is poorly defined. This study investigates how amine type and density affect the protein corona and cellular association of gold nanoparticles with cells in vitro. Four specific poly(vinyl alcohol‐co‐N‐vinylamine) copolymers are synthesized containing primary, secondary, or tertiary amines. Particle cellular association (i.e., cellular uptake and surface adsorption), as well as protein corona composition, are then investigated. It is found that the protein corona (as a consequence of “amine bulkiness”) and amine density are both important in dictating cellular association. By evaluating the nanoparticle surface chemistry and the protein fingerprint, proteins that are significant in mediating particle–cell association are identified. In particular, primary amines, when exposed on the polymer side chain, are strongly correlated with the presence of alpha‐2‐HS‐ glycoprotein, and promote nanoparticle cellular association

Artificial lysosomal platform to study nanoparticle long-term stability

Nanoparticles (NPs) possess unique properties useful for designing specific functionalities for biomedi- cal applications. A prerequisite of a safe-by-design and effective use in any biomedical application is to study NP–cell interactions to gain a better understanding of cellular consequences upon exposure. Cellular uptake of NPs results mainly in the localization of NPs in the complex environment of lysosomes, a compartment which can be mimicked by artificial lysosomal fluid. In this work we showed the applicability of lysosomal fluid as a platform for a fast assessment of gold, iron oxide and silica NP stability over 24 h in a relevant biological fluid, by using multiple analytical methods

A lock-in-based method to examine the thermal signatures of magnetic nanoparticles in the liquid, solid and aggregated states

We propose a new methodology based on lock-in thermography to study and quantify the heating power of magnetic nanoparticles. Superparamagnetic iron oxide nanoparticles exposed to a modulated alternating magnetic field were used as model materials to demonstrate the potency of the system. Both quantitative and qualitative information on their respective heating power was extracted at high thermal resolutions under increasingly complex conditions, including nanoparticles in the liquid, solid and aggregated states. Compared to conventional techniques, this approach offers a fast, sensitive and non-intrusive alternative to investigate multiple and dilute specimens simultaneously, which is essential for optimizing and accelerating screening procedures and comparative studies

Phase transformation of superparamagnetic iron oxide nanoparticles via thermal annealing: implications for hyperthermia applications

Magnetic hyperthermia has the potential to play an important role in cancer therapy and its efficacy relies on the nanomaterials selected. Superparamagnetic iron oxide nanoparticles (SPIONs) are excellent candidates due to the ability of producing enough heat to kill tumor cells by thermal ablation. However, their heating properties depend strongly on crystalline structure and size, which may not be controlled and tuned during the synthetic process; therefore, a postprocessing is needed. We show how thermal annealing can be simultaneously coupled with ligand exchange to stabilize the SPIONs in polar solvents and to modify their crystal structure, which improves hyperthermia behavior. Using high-resolution transmission electron microscopy, X-ray diffraction, Mössbauer spectroscopy, vibrating sample magnetometry, and lock-in thermography, we systematically investigate the impact of size and ligand exchange procedure on crystallinity, their magnetism, and heating ability. We describe a valid and simple approach to optimize SPIONs for hyperthermia by carefully controlling the size, colloidal stability, and crystallinity

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression